Impact of fecal carriage of extended-spectrum beta

Marmara Medical Journal 2013; 26: 127-9
DOI: 10.5472/MMJ.2013.02786.2
ORIGINAL ARTICLE/ÖZGÜN ARAŞTIRMA
Impact of fecal carriage of extended-spectrum beta-lactamase
producing Enterobacteriaceae on the outcomes of transrectal needle
biopsies of the prostate
Geniş spektrumlu beta laktamaz üreten Enterobacteriaceae taşıyıcılığının prostatın transrectal
iğne biyopsisi sonuçlarına etkisi
Elif TÜKENMEZ TİGEN, Önder ERGÖNÜL, Gülşen ALTINKANAT, Mahir ÖZGEN, Buket ERTÜRK ŞENGEL,
Zekaver ODABAŞI, Levent TÜRKERİ, Lütfiye MÜLAZIMOĞLU, Volkan KORTEN
ABSTRACT
Objective: This study aimed to address the prevalence, the risk
factors and the results of fecal carriage of extended-spectrum betalactamase producing Enterobacteriaceae (ESBL-PE) in patients
who had undergone transrectal needle biopsy of the prostate
(TRNBP).
Patients and Methods: A total of 143 patients who had
undergone TRNBP were included. Of these, 33(23%) had fecal
carriage of ESBL-PE. The mean age of the patients was 62 ± 7.5
(43-81) years.
Results: A univariate analysis showed that quinolone or other
antibiotic use within the last 2 months, prostatitis, and diabetes
mellitus (DM) were significantly associated with the presence of
ESBL-PE. A multivariate analysis showed that quinolone use within
the past 2 months (OR: 4.865; CI: 1.45-16.1), and DM (OR: 4.04;
CI: 1.64-10) were found to be significant. Development of dysuria
(p<0.001), fever (p=0.046) and chills (p=0.002) after TRNBP
were shown to be related to the presence of ESBL-PE . There was
no asymptomatic bacteriuria and sepsis, the rate of symptomatic
urinary tract infection was 19%.
Conclusion: This study showed that pre-biopsy risk factors
for the presence of ESBL-PE were quinolone or other antibiotic
use within the last 2 months and presence of DM. Changing
prophylactic regimens should not be recommended due to the low
rate of severe complications.
ÖZET
Amaç: Bu çalışmada, transrektal prostat biyopsisi (TRPB)
öncesi, hastalarda dışkıda geniş spektrumlu beta-laktamaz üreten
Enterobacteriaceae (GSBL-ÜE) taşıyıcılığı oranları, risk faktörleri
ve sonuçları gösterilmesi amaçlanmıştır.
Hastalar ve Yöntem: Toplam 143 TRPB yapılan hasta
çalışmaya alınmıştır. Bunların 33(%23)’ünde GSBL-ÜE taşıyıcılığı
bulunmuştur. Ortalama hasta yaşı 62 ± 7,5 (43-81)dir.
Bulgular: Tek değişkenli analizle son 2 ayda kinolon veya
başka bir antibiyotik kullanımı, prostatit ve diabetes mellitus
(DM) GSBL-ÜE taşıyıcılığı ile ilşkili bulunmuştur. Çok değişkenli
analiz, son 2 ayda kinolon kullanımı (OR: 4,865; CI: 1,45-16,1),
ve DM (OR: 4,04; CI: 1,64-10) varlığını önemli faktörler olarak
göstermiştir. TRPB sonrası disüri (p<0,001), ateş (p=0,046) ve
üşüme-titreme (p=0,002) gelişmesi GSBL-ÜE taşıyıcılığı ile ilişkili
bulunmuştur. Asemptomatik bakteriüri ve sepsis saptanmamıştır.
Semptomatik üriner sistem infeksiyon oranı %19’dur.
Sonuç: Bu çalışma GSBL-ÜE taşıyıcılığı için biyopsi öncesi risk
faktörlerinin son 2 ayda kinolon veya diğer antibiyotik kullanımı ve
DM varlığı olduğunu göstermiştir. Ciddi infektif komplikasyonların
düşük oranda olması nedeniyle profilaksi rejimlerinin değiştirilmesi
önerilmemektedir.
Key words: Extended-spectrum beta-lactamases, Transrectal
needle biopsy of the prostate, Fecal carriage, Infection
Introduction
Elif Tükenmez Tigen (), Buket Ertürk Şengel, Zekaver Odabaşı,
Lütfiye Mülazımoğlu, Volkan Korten
Department of Infectious Diseases and Clinical Microbiology, School of
Medicine, Marmara University, İstanbul, Turkey
e-mail: [email protected]
Önder Ergönül
Department of Infectious Diseases and Clinical Microbiology, School of
Medicine, Koc University, İstanbul, Turkey
Gülşen Altınkanat
Department of Microbiology,School of Medicine, Marmara University,
İstanbul, Turkey
Mahir Özgen, Levent Türkeri
Department of Urology, School of Medicine, Marmara Univesity, İstanbul,
Turkey
Submitted/Gönderilme: 23.06.2013 - Accepted/Kabul: 05.08.2013
Anahtar kelimeler: Geniş spektrumlu beta-laktamaz, Transrektal
prostat iğne biopsisi, Fekal taşıyıcılık, Enfeksiyon
Extended-spectrum
beta-lactamase
producing
Enterobacteriaceae (ESBL-PE) carriage is increasing
in the community, especially in elderly males in all over
the world [1,2]. Intestinal colonization is a major factor
for transmission in the community [3]. Valverde et al. have
pointed out that the prevalence of ESBL-PE infections has
increased dramatically during the last decade in Spain [2].
Moreover, an increase in the fecal carriage of E.coli that
produce ESBL from 0.1% in 2002 to 1.7% in 2005 has been
noted in the USA [4]. The incidence of fecal carriage of
ESBL-PE in Turkey was 15.2% in a recent study [5].
Transrectal ultrasound guided needle biopsy of the
prostate (TRNBP) is used by urologists to diagnose and
127
128
Tigen et al.
ESBL-PE outcomes in prostate biopsy
stage prostate cancers. Even though it is accepted as a safe
procedure, complications such as bleeding and infection can
occur. TRNBP performed without prophylactic antibiotic
administration is related to subclinical temporary bacteremia
in 73-100% of patients and to symptomatic urinary tract
infections (UTIs) in up to 87% of patients [6]. In a Swedish
study, the rates of symptomatic UTI and sepsis were reported
as 0.9% and 0.001% respectively among patients using single
dose fluoroquinolone prophylaxis [7]. Major risk factors for
development of UTI after prostate biopsies were defined
as use of corticosteroids, presence of urinary catheters,
diabetes mellitus (DM) and prostatitis [8]. We investigated
the prevalence of fecal carriage of ESBL-PE in patients
undergoing TRNBP, analyzed the risk factors for ESBL
before biopsy and described the outcome of the patients.
Patients and Methods
One hundred and forty-three patients who applied for TRNBP
at the Department of Infectious Diseases and Clinical
Microbiology, School of Medicine, Marmara University
between October 2008 and February 2010 were recruited. No
restriction was applied for the use of prophylactic antibiotics,
which were mainly quinolones, fosfomycin, aminoglycosides
and cephalosporins. The rectal swabs containing fecal
material were obtained before the biopsy and were spread
onto two MacConkey agar plates, each supplemented
with 1 µg/ml cefotaxime or 1 µg/ml ceftazidime. At least
two colonies with distinct morphotype were selected for
subsequent characterization. Combined disc method was
used to verify the ESBL production according to the Clinical
and Laboratory Standard Institute (CLSI) guidelines (CLSI,
M100-S18, Wayne, PA, USA, 2008). Urine cultures were
obtained before, 3 and 14 days after the biopsy. Symptomatic
urinary tract infection was defined as a culture positive on
the third day for any pathogen and any existing urinary tract
symptoms. Patients with 38º C fever after TRNBP were
identified as febrile. Blood cultures were obtained from the
febrile patients.
Statistical Analysis
The relationship between the fecal carriage of ESBL-PE and
post biopsy complications was analyzed using the software
SPSS for Windows, version 15.0; (SPSS Inc, Chicago,
Illinois, USA). Data obtained were presented as mean ±
SD, controlled for normal distributions by the KolmogorovSmirnov test and compared by the unpaired Student’s t-test
when the distribution appeared normal. Categorical data
between two or more groups were compared by the Pearson
χ 2 test. The effect of ESBL on the clinical outcomes was
assessed by a multivariate analysis model, where the
dependent variable was kept constant while the independent
variables changed according to the course of the follow up.
A p value of <0.05 was accepted as statistically significant.
Marmara Medical Journal 2013; 26:127-9
Results
Of the 143 patients enrolled, 33 (23%) had fecal carriage of
ESBL-PE. The mean age of the patients enrolled in the study
was 62 ± 7.5 (43-81) years. Follow-up urine cultures could
be obtained from 103 (72 %) of the patients on the 3rd day
and from 70 (49%) patients on the 14th day. Bacteriuria was
detected in 16 (15.5 %) patients on the 3rd day, there were
no growths in the urine cultures for the 14th day. Prophylaxis
of patients before biopsy was not interfered. Eighty one
(56.5%) of patients were given prophylactic fluoroquinolone,
62 (43.5%) of patients were given cefuroxime axetil.
In the univariate analysis, quinolone or other antibiotic
use within the last 2 months, prostatitis, and DM were found
to be significantly associated with the fecal carriage of the
ESBL-PE (Table I). In the multivariate analysis, quinolone
Table I. Univariate analysis of the risk factors for ESBL producing
Enterobacteriaceae carriage before biopsy
ESBL (+)
ESBL (-)
p
Quionolone use within the last
2 months
15/33 (45%) 12/110 (11%) <0.0001
Antibiotic use within the last
2 months
22/33 (67%) 31/110 (28%) <0.0001
Prostatitis
9/33 (27%) 12/110 (11%)
0.020
Hospitalization within the past
3 months
2/33 (6%)
2/110 (2%)
0.195
Urethral catheterization within
the past 2 months
1/33 (3%)
0/110
0.231
DM
8/33 (24%)
7/110 (6%)
0.003
use within the previous 2 months (OR: 4.865; CI: 1.45-16.1),
and DM (OR: 4.04; CI: 1.64-10) was found to be significantly
associated with the fecal carriage of ESBL-PE.
Development of dysuria (p<0.001), fever (p=0.046) and
chills (p=0.002) after TRNBP were found to be related with
ESBL the fecal carriage of ESBL-PE . Symptoms such as
suprapubic tenderness, hesitancy and frequency were not
found to be related with ESBL-PE.
Discussion
The increase in ESBL-PE infections after prostate biopsies
has prompted us to elucidate the possible risk factors for such
infections. Both an increase in infections and the fecal carriage
of ESBL-PE has been reported in recent studies [2, 9]. Even
though a significant number of epidemiological studies
have questioned the fecal carriage of ESBL-PE in healthy
individuals, not much information has been reported about
the specific subset of patients who received the TRNBP
procedure. In our study, the fecal carriage of ESBL-PE in
this specific group of patients was investigated.
Tigen et al.
ESBL-PE outcomes in prostate biopsy
Marmara Medical Journal 2013; 26: 127-9
The incidence of fecal carriage of ESBL-PE (in 23 % of
the patients) in our study was one of the highest among other
recent studies. The rate of fecal carriage of ESBL-PE was
reported as 7.3% in Tunisia, which is another Mediterranean
country [10]. The prevalences were reported as relatively
low in Spain (6%) [11]. However, several studies have
reported higher than Tunisia but lower than our results
(16.7%, 15.6%) [9, 12]. In a study from Turkey, the rate
of fecal carriage of ESBL-PE was reported as 15.2% [5],
whereas in our study this rate was found to be much higher.
We did not observe an increased rate of asymptomatic
bacteriuria after the biopsy in patients with ESBL-PE
carriage. In our study the symptomatic urinary tract infection
rate was 19% with no sepsis after TRNBP. The rate of sepsis
was shown to be between 0.5-2% in various studies from
different countries [13]. Our results might be related with the
limited number of patients in the study population.
Antibiotic prophylaxis for TRNBP should be given for
reducing infectious complications, although the choice of
antibiotic is not clear. Despite increasing numbers of reports
suggesting an increase of urinary tract infections (UTIs)
with ESBL producing E.coli after TRNBP, it is difficult
to recommend a major change in the current prophylaxis
practice, mainly a single dose fluoroquinolone to reduce
the number of such infections since the number of severe
infective complications is still low, as in our study.
Our results also demonstrate an independent correlation
between the fecal carriage of ESBL-PE and the presence of
DM as in previous reports [14,15]. This might be secondary
to a high rate of hospitalizations or to antibiotic usage in
diabetic patients [14]. Further large scale prospective studies
in diabetics are needed to clarify this relation.
Conclusion
In conclusion, the fecal carriage of ESBL-PE was detected
in 23 % of patients undergoing TRNBP, which is one of the
highest rates in the literature. Pre-biopsy risk factors for the
fecal carriage of ESBL-PE were quinolone or other antibiotic
use within the last 2 months and the presence of DM. A
change in prophylactic regimens cannot be recommended
due to low rate of severe complications in our study.
Acknowledgement
This study is partly supported by an Merck Sharp &
Dohme Investigator Initiated Study grant. We thank to Ms
Theresa Coque for providing control strains for CTX-M
subgroups.
129
References
1. Pitout JDD, Nordmann P, Laupland KB, et al. Emergence of
Enterobacteriaceae-producing extended-spectrum beta- lactamases
(ESBLs) in the community. J Antimicrob Chemother 2005;56:52–9.
doi: 10.1093/jac/dki166.
2. Valverde A, Coque TM, Sánchez-Moreno MP, Rollán A, Baquero
F, Cantón R. Dramatic increase in prevalence of fecal carriage of
extended-spectrum beta-lactamase-producing Enterobacteriaceae
during nonoutbreak situations in Spain. J Clin Microbiol 2004;42:476975.
3. Woerther PL, Angebault C, Jacquier H, Hugede HC. Massive increase,
spread, and exchange of extended spectrum β-lactamase-encoding
genes among intestinal Enterobacteriaceae in hospitalized children
with severe acute malnutrition in Niger. Clin Infect Dis 2011;53:67785. doi: 10.1093/cid/cir522.
4. Pallecchi L, Bartoloni A, Fiorelli C, et al. Rapid dissemination
and diversity of CTX-M extended-spectrum betalactamase genes
in commensal Escherichia coli from healthy children from lowresource settings of Latin America. Antimicrob Agents Chemother
2007;51:2720–5. doi:10.1128/AAC.00026-07.
5. Azap Kurt O, Arslan H, Karaman S, Togan T. Risk factors for fecal
carriage of extended-spectrum beta-lactamase producing Escherichia
coli and Klebsiella spp. in the community. Turk J Med Sci 2007; 37 :
31-8.
6. Thompson PM, Talbot RW, Packham DA, Dulake C. Transrectal
biopsy of the prostate and bacteraemia. Br J Surg 1980; 67:127–8.
7. Lindstedt S, Lindström U, Ljunggren E, Wullt B, Grabe M. Singledose antibiotic prophylaxis in core prostate biopsy: Impact of timing
and identification of risk factors. Eur Urol 2006;50:832-7.
8. Aus G,Ahlgren G, Bergdahl S, Hugosson J. Infection after transrectal
core biopsies of the prostate: risk factors and antibiotic prophylaxis. Br
J Urol 1996;77:851-5.
9. Valverde A, Grill F, Coque TM, et al. High rate of intestinal colonization
with extended-spectrum-beta-lactamase-producing organisms in
household contacts of infected community patients. J Clin Microbiol
2008;46:2796-9. doi: 10.1128/JCM.01008-08.
10. Ben Sallem R, Ben Slama K, Estepa V, et al. Prevalence and
characterisation of extended-spectrum beta-lactamase (ESBL)producing Escherichia coli isolates in healthy volunteers in Tunisia.
Eur J Clin Microbiol Infect Dis 2012; 31:1511-6. doi: 10.1007/
s10096-011-1471-z
11. Vinué L, Sáenz Y, Martínez S, et al. Prevalence and diversity of
extended spectrum beta-lactamases in faecal Escherichia coli isolates
from healthy humans in Spain. Clin Microbiol Infect 2009;15:954–6.
doi: 10.1111/j.1469-0691.2009.02803.x.
12. Rodriguez-Bano J, Lopez-Cerero L, Navarro MD, Diaz de Alba P.
Faecal carriage of extended-spectrum beta-lactamase-producing
Escherichia coli: prevalence, risk factors and molecular epidemiology.
J Antimicrob Chemother 2008;62:1142-9. doi: 10.1093/jac/dkn293.
13. Ruddick F, Sanders P, Bicknell SG, Crofts P. Sepsis rates after
ultrasound-guided prostate biopsy using a bowel preparation protocol
in a community hospital. J Ultrasound Med 2011;30:213-6.
14. Silva N, Oliveira M, Bandeira AC, Brites C. Risk factors for
infection by extended-spectrum beta-lactamase producing Klebsiella
pneumoniae in a tertiary hospital in Salvador, Brazil. Braz J Infect Dis
2006;10:191-3.
15. Rodriguez-Bano J, Navarro MD, Romero L, et al. Epidemiology
and clinical features of infections caused by extended-spectrum betalactamase-producing escherichia coli in nonhospitalized patients. J
Clin Microbiol 2004;42:1089-94.